A major limitation with the contemporary vaccination program as a preventative measure against tetanus is the encumbrance associated with multiple needle-dependent injections. Our aim is to develop a simple method for the delivery of tetanus vaccines by topical application of an adenovirus-vectored vaccine patch. The hypothesis is that the expression of the tetanus toxin C-fragment (tetC) in the outer layer of skin can induce a systemic immune response against the toxin molecule. We have demonstrated that a protective immune response against live Clostridium tetani infection could be elicited in mice by a single topical application of a patch containing an adenovirus vector encoding tetC. These studies will further develop the vectored vaccine patch, and specifically determine whether this novel approach for the delivery of vaccines can mobilize the immune repertoire against tetanus in humans. In this project, the potential for a vectored vaccine patch to elicit a protective immune response against tetanus in animals with pre-existing immunity to adenovirus will be investigated. A new generation of adenovirus vectors with reduced immunogenicity as well as enhanced transduction efficiency for the outer layer of skin will be developed as novel vaccine carriers. Efficacy of NIVS will be compared to those induced by other means. The interaction between vectors and the host will be studied by determining the fate of vector DNA. A Phase I human clinical trial for evaluating the safety of a vectored vaccine patch will be conducted. The overall goal of these experiments is to determine whether tetanus vaccines can be effectively and safely delivered by a skin patch that requires a lower level of skill in a needle-free manner. PROPOSED COMMERCIAL APPLICATION: Non-invasive vaccination onto the skin may boost vaccine coverage against tetanus because the procedure is simple, effective, painless, and safe, The development may also make vaccination programs less dependent upon medical resources.